Microfluidic cell and method for sample handling

ABSTRACT

The present invention relates to a microfluidic cell and method for sample handling, and more particularly a cell (1) with a one-dimensional or two-dimensional array of ultrasonic transmitters (2) or resonance cavities for trapping biologically activated microbeads and passing fluids carrying samples interacting with the microbeads for detection and analysis. The invention allows for individual loading of the positions in the cell and individual detection steps enabling multistep biological assays to be performed on submicrolitre volumes. The invention also relates to an apparatus and method for blood plasma analysis incorporating such a microfluidic cell.

FIELD OF THE INVENTION

The present invention relates to a microfluidic cell and method forsample handling, and more particularly a cell with a one-dimensional ortwo-dimensional array of ultrasonic transmitters or resonance cavitiesfor trapping biologically activated microbeads and passing fluidscarrying samples interacting with the microbeads for detection andanalysis. The invention allows for individual loading of the positionsin the cell and individual detection steps enabling multistep biologicalassays to be performed on submicrolitre volumes. The invention alsorelates to an apparatus and method for blood plasma analysisincorporating such a microfluidic cell.

STATE OF THE ART

Future microfluidic systems for handling of microparticles and beadsdemand fast individual handling and analysis with minimum ofregeneration and inflexible chemistry. The proposed ultrasonic arraysystem solves several problems encountered in prior related techniqueslike optical tweezers and trapping by means of dielectrophoretic forces.In optical tweezers the trapping force is by orders of magnitude smallerwhich makes it impossible to trap larger clusters of beads as well asreduces the maximum liquid flow rate. Dielectrophoretic trapping islimited by the dielectric characteristics of the trapped particles anddemands electrodes that generate the electric field as well as generatea current through the medium.

In the proposed ultrasonic array system, a chemically or biologicallyactive material, e.g. activated microbeads or living cells, will betrapped in the centre of a flow channel and will be kept away from thewalls. Thus there will be no need for coupling chemistry or mechanicalmeans for the immobilisation of the active material. Regeneration of thesystem will therefore be simple which will lead to a versatile systemsince the functionality is determined by the chemical functionalisationof the bead surface.

SUMMARY OF THE INVENTION

According to a first aspect of the invention, there is provided amicrofluidic cell having an inlet and an outlet for fluid flow through achannel, characterised by an array of ultrasonic transmitter unitsarranged at separate positions between the inlet and the outlet; and acontrol unit for controlling the operation of the array and adapted toactivate the transmitter units to create an acoustic radiation pressureat selected transmitter unit positions.

According to a second aspect of the invention, the microfluidic cell mayhave multiple inlets and outlets for fluid flow through multiplechannels, with a first inlet side with inlets for fluid flow in a firstdirection towards outlets at a first outlet side, a second inlet sidewith inlets for fluid flow in a second direction towards outlets at asecond outlet side, the first direction being essentially orthogonal tothe second direction; an array of ultrasonic transmitter units beingarranged at separate positions between the inlet and the outlet sides;and a control unit for controlling the operation of the array andadapted to activate the transmitter units to create an acousticradiation pressure at selected transmitter unit positions.

According to a third aspect of the invention, there is provided amicrofluidic cell having inlets and outlets for fluid flow throughchannels, characterised by a first inlet side with inlets for fluid flowin a first direction towards outlets at a first outlet side, a secondinlet side with inlets for fluid flow in a second direction towardsoutlets at a second outlet side, the first direction being essentiallyorthogonal to the second direction; a number of separate acousticradiation pressure trapping positions between the inlet and the outletsides; and at least one ultrasonic transmitter unit arranged to createan acoustic radiation pressure at at least one trapping position.

According to a fourth aspect of the invention, there is provided anapparatus suitable for plasma analysis incorporating such a microfluidiccell.

According to a fifth aspect of the invention, there is provided a methodfor sample handling using a microfluidic cell having an inlet and anoutlet for fluid flow through a channel, an array of ultrasonictransmitter units arranged at separate positions between the inlet andthe outlet; and a control unit for controlling the operation of thearray and adapted to activate the transmitter units to create anacoustic radiation pressure at selected transmitter unit positions,characterised by the steps of:

-   -   loading the cell with active material;    -   passing fluid carrying a sample to be analysed through the        channel;    -   letting the sample interact with the active material.

According to a sixth aspect of the invention, there is provided a methodfor sample handling using a microfluidic cell having multiple inlets andoutlets for fluid flow through channels, with a first inlet side withinlets for fluid flow in a first direction towards outlets at a firstoutlet side, a second inlet side with inlets for fluid flow in a seconddirection towards outlets at a second outlet side, the first directionbeing essentially orthogonal to the second direction; an array ofultrasonic transmitter units arranged at separate positions between theinlet and the outlet sides; and a control unit for controlling theoperation of the array and adapted to activate the transmitter units tocreate an acoustic radiation pressure at selected transmitter unitpositions, characterised by the steps of:

-   -   loading the cell with active material in the first direction;    -   passing fluid carrying a sample to be analysed through the        channels in the second direction;    -   letting the sample interact with the active material.

According to a seventh aspect of the invention, there is provided amethod for sample handling using a microfluidic cell having inlets andoutlets for fluid flow through channels, with a first inlet side withinlets for fluid flow in a first direction towards outlets at a firstoutlet side, a second inlet side with inlets for fluid flow in a seconddirection towards outlets at a second outlet side, the first directionbeing essentially orthogonal to the second direction; a number ofseparate acoustic radiation pressure trapping positions between theinlet and the outlet sides; and at least one ultrasonic transmitter unitarranged to create an acoustic radiation pressure at at least onetrapping position, characterised by the steps of:

-   -   loading the cell with active material in the first direction;    -   passing fluid carrying a sample to be analysed through the        channels in the second direction;    -   letting the sample interact with the active material

According to a eighth aspect of the invention, there is provided amethod for plasma analysis incorporating such a microfluidic cell.

The invention is defined in the independent claims 1, 2, 12, 25, 28, 29,42 and 51, while preferred embodiments are set forth in the dependentclaims.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be described in detail below with reference to theaccompanying drawings, of which:

FIG. 1 is an exploded view in perspective, partly cut-away, of atwo-dimensional cell according to the present invention,

FIG. 2 is a cross-section of the cell in FIG. 1,

FIGS. 3A and 3B are schematic illustrations of the loading flow andanalytical flow in one embodiment of the method of the invention,

FIGS. 4A and 4B are schematic illustrations from above and inperspective of one design of a resonance cavity in one embodiment of theinvention,

FIGS. 5A and 5B are schematic illustrations from above and inperspective of another design of a resonance cavity in one embodiment ofthe invention,

FIG. 6 is a schematic illustration of a channel grid in one embodimentof the invention, and

FIGS. 7A, 7B and 7C are schematic illustrations of various designs ofexcitation elements according embodiments of the present invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

This application outlines the development of a new microfluidic platformfor miniaturised sample handling in array formats ultimately for 2D(two-dimensional) large-scale parallel analysis of biological samplese.g. screening. A special case is a one-dimensional cell with only onechannel and a one-dimensional array of ultrasonic transmitter trappingpositions. The use of ultrasonic trapping of biologically activatedmaterial e.g. microbeads in a microscaled array format will enableadvanced multistep biological assays to be performed on submicrolitresample volumes. The system can be viewed as a generic platform forperforming any microbead based bioassay in an array format. Thedescribed ultrasonic based microbead trapping and spatially controlledtransport of the beads in the assay area of the microsystem is a keyconcept which in conjunction with microdomain laminar sheet flow offersa 2D-format for the analysis system. As multiple analytical techniquescan be employed for the signal readout e.g. electrochemical simultaneouswith optical (fluorescence—CCD-imaging), a wealth of information fromthe assay may be collected.

The invention is described with microbeads as an example of activematerial. Generally, the active material may be biologically orchemically activated micro/nanoparticles including beads, cells, spores,and bacteria. The beads may be biologically activated by means of e.g.antibodies or oligonucleotides for selective binding of targetedbiomolecules, that is antigens and DNA.

The invention provides a fluid cell fabricated by means ofmicro/nanotechnology for microparticle manipulation and analysis withall the necessary electronics, sensors etc. Real biomolecules can behandled, detected and separated.

A microscale flow cell 1 according to one embodiment of the inventionthat uses an actuator or transducer surface divided in severalseparately addressable “pixels” or ultrasonic trapping elements 2 in anarray format is shown in FIGS. 1 and 2. Each element 2 can beindependently controlled to trap particles/beads and throughco-operation of several elements 2 it will be possible to transport thetrapped particles over the array area. Each element 2 can be driven byan AC-signal where the frequency is selected to form a standing wavebetween the element 2 and the lid 3 of the flow cell 1. An acousticradiation force array is thus formed where particles/beads can betrapped above each element.

The device could be described as a sealed “square” with several inlets4, 5 and outlets 6, 7 forming two orthogonal flow paths as shown by thearrows 8, 9. There are no internal walls between the flow paths in thesealed square. The square will have particular positions for detectionand analysis and in a subsequent step the particles may be transportedto the proper outlet for further analysis, enrichment etc.

The flow cell will have a channel height that allows for a standing wavepattern with one or several velocity anti-nodes, separated by half thewavelength (λ/2) of the ultrasound in the fluid. The standing wavepattern creates an acoustic radiation trapping force either in thevelocity anti-nodes or nodes depending on the properties of the mediaand particle properties. The force is proportional to the frequency. Forinstance, at an excitation frequency of a few MHz the height of the flowcell will typically be in the millimetre to micrometer range. Apiezoelectric PZT transducer array with 250 μm elements arranged in a 10by 10 array would typically occupy an area of 3 mm by 3 mm. The systemvolume would thus typically occupy 10 nL/bead coordinate. Higherultrasound frequencies may be superimposed for sensing purposes.

The channel height allows for laminar flows through the cell duringoperation with normal flow velocities. Thus, there is no mixing of thedifferent liquids except for a very limited diffusion region along theborderline between each parallel flow line. However, it is possible toachieve non-laminar flows by increasing the flow rate in selectedchannels. This can be exploited to mix channels in a desired way.

The actuator surface is preferably a micromachined piezoelectricmultilayer structure consisting of sub-millimetre-sized (e.g. 250micrometer) pixels with integrated impedance matching and backinglayers/structures. The are several reasons for using a multilayerstructure instead of a piezoelectric plate, e.g. it is easier to matchelectric and acoustic impedance, the drive voltages are reduced and itis easier to improve heat conduction from the transducer. Still for lessdemanding devices more conventional diced piezoelectric plates can beused as transducers. Micromachining of the actuator structure allows forparticular solutions to impedance matching that is important foractuation as well as sensing functions. By introduction of void volumesin the actuator structure, the acoustic impedance is better matched withaqueous fluids.

To trap the beads the acoustic intensity has to be focused spatially andseveral techniques, such as focussing surfaces, mainly on the undersideof the lid, and phase shifting between pixels, will be provided. Theheating caused by inevitable losses in the material should be minimisedand one embodiment of the invention will use integrated cooling channels(not shown). In general the heat conduction is improved by allowing heattransport in the electrical vias, electrodes and pattern.

The actuator array may be fabricated in several actuatormaterials/devices, e.g. piezoelectric, electrostrictive, relaxor,magnetostrictive, polymer, ceramics and silicon allowing forthree-dimensional microstructuring of the active material. To preparefor an easy and individual contacting of the pixels, a verticalelectrical via-patterning can be made. The piezoelectric elements may beembedded in a silicon or polymer substrate 11 with an air-gap, lowacoustic impedance or dampening material 10 surrounding eachpiezoelectric element. A convenient way of building the transducer arrayis to use a flexible printed circuit board as the matching layer betweenthe fluid cell and the array elements. The circuit board may compriseadditional polymer films laminated on top of the transducer surfaceisolating the substrate 11 from the liquid and acting as a furtheracoustic impedance match. The thickness is well controlled and theelectrical pattern can be made on the side facing the transducer array.All contacts to the transducer units of the transducer array may bearranged on the top side of the transducer units. Alternatively, onepole of each transducer unit is one the top and the other at the bottomin contact with the substrate. This simplifies the assembling and givesmore freedom regarding heat transport and electrical connections.

The liquid cell will typically have a micromachined glass or polymer lid3 sealed to the active surface. The transparent lid will at the sametime be a reflector for the ultrasonic semi-standing waves and a windowfor optical or a carrier for micro-electrodes for electrochemicaldetection. The lid may be provided with focussing surfaces on theunderside e.g. shallow cup-shaped cavities over each ultrasonictransmitter position.

In an alternative embodiment, the lid comprises an actuator array oftransducer units so that the microfiuidic cell is formed of pairs ofopposing transducer units. This embodiment is capable of generatingparticularly strong acoustic trapping forces.

The lid may comprise transparent windows at desired positions to whichmaterial is moved for detection by controlling the flows and/or theoperation of the transducer units. It is also possible to use the cellwithout any detection step in case a well-defined process is run. Inthis case, samples typically interact with active material atpredetermined positions, and the material at these positions iscollected and released from the cell for further processing outside thecell. Typical applications are purification processes.

The primary types of sensors considered for analysis inside the squareare based on optical and electrochemical techniques while the acousticdetection is mainly intended for detection of the presence of bead ornot during the loading of the cell. The acoustic manipulation as well asthe ultrasonic detection will however in some cases give additionalinformation. The transport properties during manipulation will be onepossible parameter for separation and combining this with the sensorinformation makes it possible to make separations in several differentways.

An example of the cell operation is illustrated in FIGS. 3A and 3B.Prior to the analysis step the cell is loaded by supplying differentbead flows 8 to the channels through the inlets 4 (A, B, . . . , X) tothe left. By switching on the ultrasound the beads are trapped inpositions 2 set by the transducer array. The downstream positions areloaded first. It is possible to arrange the same type of beadsthroughout the whole cell, or different types in different channels, oreven different types at each individual position depending on theparticular application.

The analytical flows 9 carrying samples to be analysed is then suppliedorthogonally to the bead flow through the inlets 5 (A, B, . . . , Y) tothe right. Each laminar sample flow line passes each orthogonal flowline A-X, with different or the same types of beads, as the case may be.The cell may then be subjected to a detection procedure. For instance,the cell is illuminated and the fluorescence signal is detected by e.g.a CCD-camera or a fluorescence microscope. Since the microscale flow isalways laminar there is no mixing of the different liquids except for avery limited diffusion region along the borderline between the eachsample line 9.

After the detection, identified samples may be transported betweenpositions in the cell. This is achieved by operating the ultrasonictransmitters, switching them on and off and/or using phase-shiftingbetween positions. For instance, lowering the intensity at one positionand increasing the intensity at another neighbouring position will movethe material from the first to the latter position. The effect exists inthe absence of any flow and even counter to the flow. Instead oflowering the intensity, the frequency may be changed to remove theresonance condition which has the effect of removing the trapping forceat that position. Also, flows may be supplied through selected inlets 4and 5. Samples may be collected in a common flow line, and the collectedsamples may then be released from the cell by switching off theultrasonic transmitters in the desired flow line for further analysis orprocessing outside the cell.

The transportation of beads by sequentially switching the acoustic fieldalong the transducer array has to be well controlled. The electronicscontrol of the individual pixels should be as simple as possible withoutrisks for bead loss. To increase the manipulation control the sensingfunction of the pixels can be used to verify a successful movement.Transportation over longer distances than between two pixels can beconsidered as repetitions of a one-pixel step.

A simplified embodiment of the invention comprises a cell with only onechannel, i.e. a one-dimensional cell. A cross-section will be as shownin FIG. 2. In this case the loading flow and the analytical flow are notorthogonal to each other but flows along one and the same channel.However, by loading the cell with different types of active material,starting with the farthest down-stream position, it is possible toobtain a diversity, in that the analytical flow is subjected todifferent bioactive interactions when flowing through the channel.

It is also possible to obtain a separation orthogonal to the activetransducer surface plane, i.e. in the height direction. By selecting theultrasonic frequency such that the channel height corresponds to morethan one velocity anti-node several clusters of beads are trapped aboveeach ultrasonic transmitter. The laminar flow of the liquid will alsoallow for a three dimensional manipulation and analysis. The inlets andoutlets are provided with separate channels enabling independent laminarflows at different heights of the cell in addition to the orthogonalflow directions. Thus, samples at different height positions can bemoved by liquid flow at different heights or groups of samples trappedabove each other can be moved at the same time. For instance, a channelheight of 300 μm can accommodate six channels each 50 μm high. Frequencymodulations and phase modulations changes the acoustic radiationpressure at the different nodes and the trapping sites above each arraypixel can therefore be controlled more or less individually.

Further embodiments of the invention is shown in FIGS. 4AB to 7A-C. Themain difference to the previous embodiments is that the interior of thecell is not open but comprises a channel grid structure with wallsbetween channels. Each crossing point in the channel grid forms aresonance cavity. An acoustic radiation pressure is produced by means ofacoustic resonance in the horizontal direction in the resonance cavitybetween the walls at the crossing points between the channels. Theresonance cavities will have a channel width that allows for a standingwave pattern with one or several velocity anti-nodes, separated by halfthe wavelength (λ/2) of the ultrasound in the fluid. Also the height ofthe channels may be adapted to fulfil the resonance condition so that anincreased trapping force acting on the particles is obtained.

Two designs of resonance cavities 21, 21′ are shown in FIGS. 4A, 4B and5A, 5B, respectively. The cavity is defined by four vertical opposingwalls between which standing waves 22 are produced in two or moredirections U-U′ and V-V′ as is shown by the dotted lines. Two crossingflows are generally passing through the cavity. In FIG. 4AB the wallsare straight giving rise to a planar standing wave in two directions. InFIG. 5AB the walls are circular segments giving rise to circularsymmetric standing waves.

In alternative embodiments, a cavity may be provided with a greaternumber of inlets and outlets than shown in the figures. For example,three flows may cross in a cavity. Also, in some applications the numberof inlets to the cavity need not be equal with the number of outlets.Furthermore, the angle between flows need not orthogonal in ageometrical sense, but any practical angle may be used.

As is shown in FIG. 6, a number of resonance cavities 21 (straight orcircular symmetric) may be combined with communicating connectionchannels 23 into a grid in which each crossing defines an analysisposition where e.g. biospecific microparticles (microbeads) are trapped.In analogy with the previous embodiments, the cell thus comprises firstand second inlet sides 4′, 5′ and first and second outlet sides 6′, 7′.The first inlets and outlets are associated with rows A-X, and thesecond inlets and outlets are associated with rows A-Y. For example,each row A-X of the grid may define a particle type and by letting eachorthogonal channel A-Y define a sample flow (e.g. a blood plasma sample)a multi-analysis chip is obtained.

The standing waves are produced by exciting the cell by means of one ormore excitation elements or transducers of the types discussed above.The shape and design may be varied for instance as is shown in FIGS.7A-C described below.

In FIG. 7A one excitation element 24A covers the whole channel grid andexcites all positions at the same time. In FIG. 7B there is oneexcitation element 24B for each position 21 (resonance cavity). Bydesigning the chip in a suitable way the excitation of one individualcavity will not interfere with neighbouring cavities. Thus, eachposition can be excited individually. FIG. 7C shows a combination of anelement 24C exciting several positions with individual element 24Dexciting individual positions. It is also possible to use an excitationelement that only covers part of the grid (not shown) without excitingthe remainder of the positions.

One contemplated application of the microfluidic cell according to theinvention is analysis of blood plasma. The microfluidic cell isincorporated in an apparatus comprising a blood plasma separator forreceiving a blood sample and separating the plasma for analysis. Asuitable blood plasma separator is described in PCT/SE02/00428 (not yetpublished). A microprocessor-based control unit controls the operationof the transducer array and various pumps supplying flows through thecell. The apparatus may be designed as a portable bedside device. Themicrofluidic cell is preferably exchangeable and provided as adisposable product.

A number of vials or a cassette containing active material especiallyprepared for the desired, often standardised, analysis is connected tothe inlets 4 for loading the cell. The microfluidic cell is connected toreceive the separated plasma at the inlets 5 for the analytical flow.When the cell is started an automatic loading procedure is performedbringing active material to predetermined positions in the cell by meansof pumps and controlling the transducer array to switch on trappingforces in a programmed time sequence. The loading step will only take afew seconds or less. In the meantime, a blood sample is collected from apatient and the plasma is separated. A blood sample volume of 0.5 ml orless will be sufficient and can be collected together with a sample forother conventional tests. Then the analytical flow containing the plasmais brought through the cell interacting with the active material independence of the contents of the plasma. The interaction step will onlytake a few seconds or less. The detection procedure is then startedperforming an automatic scanning of the different positions and e.g.looking for presence or absence of reactions. The apparatus may beconnected to a data system for storing and/or printing the results ofthe analysis.

The scope of the invention is only limited by the claims below.

1-51. (canceled)
 52. A microfluidic cell having an inlet and an outletfor fluid flow through a channel, comprising an array of ultrasonictransmitter units arranged at separate positions between the inlet andthe outlet, each ultrasonic transmitter unit capable of beingindependently controlled to create an acoustic ultrasonic radiationpressure; and a control unit for controlling the operation of the arrayand adapted to activate selected transmitter units to create an acousticradiation pressure at selected transmitter unit positions; and in thatthe channel height is of the same order as the ultrasonic wavelength ofthe fluid.
 53. A microfluidic cell according to claim 52, wherein theultrasonic transmitter units are piezoelectric elements.
 54. Amicrofluidic cell according to claim 53, wherein the piezoelectricelements are embedded in a silicon or polymer substrate.
 55. Amicrofluidic cell according to claim 52, wherein the ultrasonictransmitter units are polymer actuators.
 56. A microfluidic cell havinginlets and outlets for fluid flow through channels, comprising a firstinlet side with inlets for fluid flow in a first direction towardsoutlets at a first outlet side, a second inlet side with inlets forfluid flow in a second direction towards outlets at a second outletside, the first direction being essentially orthogonal to the seconddirection; an array of ultrasonic transmitter units arranged at separatepositions between the inlet and the outlet sides, each ultrasonictransmitter unit capable of being independently controlled to create anacoustic ultrasonic radiation pressure; and a control unit forcontrolling the operation of the array and adapted to activate selectedtransmitter units to create an acoustic radiation pressure at selectedtransmitter unit positions; and in that the channel height is of thesame order as the ultrasonic wavelength of the fluid.
 57. A microfluidiccell according to claim 56, wherein the ultrasonic transmitter units arepiezoelectric elements.
 58. A microfluidic cell according to claim 57,wherein the piezoelectric elements are embedded in a silicon or polymersubstrate.
 59. A microfluidic cell according to claim 56, wherein theultrasonic transmitter units are polymer actuators.
 60. A microfluidiccell according to claim 52, wherein the cell comprises a transparentlid.
 61. A microfluidic cell according to claim 60, wherein the lid ismade of glass or polymer.
 62. A microfluidic cell according to claim 60,wherein the lid is provided with sound reflecting surfaces arranged atthe transmitter unit positions.
 63. A microfluidic cell according toclaim 52, wherein the cell comprises a lid with an actuator array oftransducer units.
 64. A microfluidic cell according to claim 56, whereinthe cell comprises a lid with an actuator array of transducer units. 65.A microfluidic cell according to claim 63, wherein the lid comprisestransparent windows.
 66. A microfluidic cell according to claim 64,wherein the lid comprises transparent windows.
 67. A microfluidic cellaccording to claim 63, wherein the lid is provided with sound reflectingsurfaces arranged at the transmitter unit positions.
 68. A microfluidiccell according to claim 52, wherein the control unit is adapted toactivate the transmitter units to create an acoustic radiation pressurecapable of moving material between selected transmitter unit positions.69. A microfluidic cell according to claim 56, wherein the control unitis adapted to activate the transmitter units to create an acousticradiation pressure capable of moving material between selectedtransmitter unit positions.
 70. A microfluidic cell having inlets andoutlets for fluid flow through channels, comprising a first inlet sidewith inlets for fluid flow in a first direction towards outlets at afirst outlet side, a second inlet side with inlets for fluid flow in asecond direction towards outlets at a second outlet side, the firstdirection crossing the second direction; a number of separate acousticradiation pressure trapping positions between the inlet and outletsides; and at least one ultrasonic transmitter unit arranged to createan acoustic radiation pressure at at least one trapping position; and inthat the channel height is of the same order as the ultrasonicwavelength of the fluid.
 71. A microfluidic cell according to claim 70,wherein the cell comprises a channel grid structure with walls betweenchannels, and each crossing point in the channel grid forms a resonancecavity.
 72. A microfluidic cell according to claim 71, wherein anacoustic radiation pressure is produced by means of acoustic resonancein the horizontal direction in the resonance cavity.
 73. A microfluidiccell according to claim 72, wherein the resonance cavity is defined bystraight vertical opposing walls between which standing waves may beproduced.
 74. A microfluidic cell according to claim 72, wherein theresonance cavity is defined by circular segments.
 75. A microfluidiccell according to claim 70, further comprising one excitation elementarranged to cover the whole channel grid and excite all trappingpositions at the same time.
 76. A microfluidic cell according to claim75, wherein the excitation elements are piezoelectric elements orpolymer actuators.
 77. A microfluidic cell according to claim 70,further comprising one excitation element arranged to cover part of thechannel grid.
 78. A microfluidic cell according to claim 77, wherein theexcitation elements are piezoelectric elements or polymer actuators. 79.A microfluidic cell according to claim 70, further comprising oneexcitation element for each trapping position.
 80. A microfluidic cellaccording to claim 79, wherein the excitation elements are piezoelectricelements or polymer actuators.
 81. A microfluidic cell according toclaim 70, further comprising a combination of an excitation elementexciting several trapping positions with individual excitation elementsexciting individual trapping positions.
 82. A microfluidic cellaccording to claim 81, wherein the excitation elements are piezoelectricelements or polymer actuators.
 83. A microfluidic cell according toclaim 52, wherein the channel height is selected to produce a standingwave pattern.
 84. A microfluidic cell according to claim 56, wherein thechannel height is selected to produce a standing wave pattern.
 85. Amicrofluidic cell according to claim 70, wherein the channel height isselected to produce a standing wave pattern.
 86. A microfluidic cellaccording to claim 52, wherein the ultrasonic frequency is in the MHzrange.
 87. A microfluidic cell according to claim 56, wherein theultrasonic frequency is in the MHz range.
 88. A microfluidic cellaccording to claim 70, wherein the ultrasonic frequency is in the MHzrange.
 89. A microfluidic cell according to claim 52, wherein the inletsand outlets are provided with separate channels enabling independentlaminar flows at different heights of the cell.
 90. A microfluidic cellaccording to claim 56, wherein the inlets and outlets are provided withseparate channels enabling independent laminar flows at differentheights of the cell.
 91. A microfluidic cell according to claim 70,wherein the inlets and outlets are provided with separate channelsenabling independent laminar flows at different heights of the cell. 92.An apparatus suitable for plasma analysis comprising a microfluidic cellaccording to claim
 52. 93. An apparatus suitable for plasma analysiscomprising a microfluidic cell according to claim
 70. 94. An apparatusaccording to claim 92, further comprising a blood plasma separator forreceiving a blood sample and separating the plasma for analysis; amicroprocessor-based control unit for controlling the operation of thetransducer array and various pumps supplying flows through the cell. 95.An apparatus according to claim 94, further comprising a containercontaining active material connected to the inlets for loading the cell.96. An apparatus according to claim 93, further comprising a bloodplasma separator for receiving a blood sample and separating the plasmafor analysis; a microprocessor-based control unit for controlling theoperation of the transducer array and various pumps supplying flowsthrough the cell.
 97. An apparatus according to claim 96, furthercomprising a container containing active material connected to theinlets for loading the cell.
 98. A method for sample handling using amicrofluidic cell having an inlet and an outlet for fluid flow through achannel, an array of ultrasonic transmitter units arranged at separatepositions between the inlet and the outlet; and a control unit forcontrolling the operation of the array and adapted to activate thetransmitter units to create an acoustic radiation pressure at selectedtransmitter unit positions, comprising the steps of: loading the cellwith active material; passing fluid carrying a sample to be analyzedthrough the channel; letting the sample interact with the activematerial.
 99. A method according to claim 98, wherein the loading stepcomprises trapping the active materials at selected transmitter unitpositions by means of the acoustic radiation pressure.
 100. A methodaccording to claim 99, wherein active material of different types aretrapped at different selected transmitter unit positions.
 101. A methodaccording to claim 99, wherein the trapped active material is releasedtogether with the sample for further processing.
 102. A method forsample handling a microfluidic cell having inlets and outlets for fluidflow through channels, with a first inlet side with inlets for fluidflow in a first direction towards outlets at a first outlet side, asecond inlet side with inlets for fluid flow in a second directiontowards outlets at a second outlet side, the first direction beingessentially orthogonal to the second direction; an array of ultrasonictransmitter units arranged at separate positions between the inlet andthe outlet sides; and a control unit for controlling the operation ofthe array and adapted to activate the transmitter units to create anacoustic radiation pressure at selected transmitter unit positions,comprising the steps of: loading the cell with active material in thefirst direction; passing fluid carrying a sample to be analyzed throughthe channels in the second direction; letting the sample interact withthe active material.
 103. A method according to claim 102, wherein theloading step comprises trapping the active materials at selectedtransmitter unit positions by means of the acoustic radiation pressure.104. A method according to claim 103, wherein active material ofdifferent types are trapped at different selected transmitter unitpositions.
 105. A method according to claim 102, wherein the loadingstep comprises passing flows with active material of different typesthrough different channels in the first direction.
 106. A methodaccording to claim 105, wherein the step of passing fluids furthercomprises carrying different samples through different channels in thesecond direction.
 107. A method according to claim 102, wherein thetrapped active material is released together with the sample for furtherprocessing.
 108. A method according to claim 102, wherein the trappedactive material in a channel in the second direction is releasedtogether with the sample for further processing.
 109. A method accordingto claim 102, wherein active material together with sample are movedbetween selected transmitter unit positions.
 110. A method according toclaim 109, wherein samples are moved by varying the intensities of thetransmitters close to the sample position.
 111. A method according toclaim 110, wherein active material together with samples are moved to becollected in a common channel, and the trapped active material in thechannel is released together with the samples for further analysis orprocessing.
 112. A method according to claim 98, wherein the cell isloaded with active material in the form of bioactive microbeads.
 113. Amethod according to claim 102, wherein the cell is loaded with activematerial in the form of bioactive microbeads.
 114. A method according toclaim 98, wherein the cell is subjected to a detection procedure.
 115. Amethod according to claim 102, wherein the cell is subjected to adetection procedure.
 116. A method according to claim 114, wherein thedetection procedure comprises scanning the transmitter unit positions bymeans of a CCD camera or a fluorescence microscope.
 117. A methodaccording to claim 115, wherein the detection procedure comprisesscanning the transmitter unit positions by means of a CCD camera or afluorescence microscope.
 118. A method for sample handling using amicrofluidic cell having inlets and outlets for fluid flow throughchannels, with a first inlet side with inlets for fluid flow in a firstdirection towards outlets at a first outlet side, a second inlet sidewith inlets for fluid flow in a second direction towards outlets at asecond outlet side, the first direction crossing the second direction; anumber of separate acoustic radiation pressure trapping positionsbetween the inlet and the outlet sides; and at least one ultrasonictransmitter unit arranged to create an acoustic radiation pressure at atleast one trapping position comprising the steps of: loading the cellwith active materials in the first direction; passing fluid carrying asample to be analyzed through the channels in the second direction;letting the sample interact with the active material.
 119. A methodaccording to claim 118, wherein active material of different types aretrapped at different selected trapping positions.
 120. A methodaccording to claim 118, wherein the loading step comprises passing flowswith active material of different types through different channels inthe first direction.
 121. method according to claim 120, wherein thestep of passing fluids further comprises carrying different samplesthrough different channels in the second direction.
 122. A methodaccording to claim 119, wherein the trapped active material is releasedtogether with the sample for further processing.
 123. A method accordingto claim 119, wherein the trapped active material in a channel in thesecond direction is released together with the sample for furtherprocessing.
 124. A method according to claim 118, wherein the cell isloaded with active material in the form of bioactive microbeads.
 125. Amethod according to claim 118, wherein the cell is subjected to adetection procedure.
 126. A method according to claim 125, wherein thedetection procedure comprises scanning the transmitter unit positions bymeans of a CCD camera or a fluorescence microscope.
 127. A method forplasma analysis incorporating a microfluidic cell according to claim 52comprising the steps of: loading the cell by bringing active material topredetermined positions in the cell; collecting plasma; bringing ananalytical flow containing the plasma through the cell; letting theanalytical flow interact with the active material; performing adetection procedure scanning the different positions in the cell.
 128. Amethod for plasma analysis incorporating a microfluidic cell accordingto claim 56 comprising the steps of: loading the cell by bringing activematerial to predetermined positions in the cell; collecting plasma;bringing an analytical flow containing the plasma through the cell;letting the analytical flow interact with the active material;performing a detection procedure scanning the different positions in thecell.
 129. A method for plasma analysis incorporating a microfluidiccell according to claim 70 comprising the steps of: loading the cell bybringing active material to predetermined positions in the cell;collecting plasma; bringing an analytical flow containing the plasmathrough the cell; letting the analytical flow interact with the activematerial; performing a detection procedure scanning the differentpositions in the cell.